Antipsychotics for children and young adults: a comparative effectiveness review

Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ≤24 years with psychiatric and behavioral conditions. We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate. Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome). This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed.